The overall goal of this project is to examine and characterize hormonal sensitivity and growth control of tumor cells in the context of a working hypothesis suggesting that oncogenic transformation may result from a selective increase in sensitivity to external regulators. Two different kinds of erythroleukemia populations have been analyzed. In the first, hematopoietic cells were infected in vitro with two strains of Friend virus. Both variants induce erythroid bursts that proliferated and differentiated without added erythropoietin (Epo). However, while the bursts induced by FVP were well "hemoglobinized" (i.e., most cells contained hemoglobin), the cells of FVA-induced bursts contained little or no hemoglobin. The nonhemoglobin bursts, induced by FVA, were established to be erythroid by cytochemistry, electron microscopy, and hormone sensitivity. FVA-induced cells appeared to be hypersensitive to Epo since small concentrations of the hormone produced marked increases in hemoglobin production--even when the hormone was added to the cultures three days post-infection. Time-lapse photography documented that Epo-stimulated hemoglobin synthesis in virally transformed cells rather than uninfected erythroid precursors. Upon reexamination FVP-induced erythroid cells also were hypersensitive to Epo. These data are consistent with the hypothesis that oncogenic transformation may result from increased sensitivity of progenitor cells for natural, physiological regulators. The second erythroleukemia population was induced in vitro by Friend murine leukemia virus (F-MuLV). When placed into cultures these erythroleukemia cells need Epo for their growth. By reducing the Epo levels in vivo, survival time of the erythroleukemia could be greatly extended. These results suggest antihormone therapy may be effacacious for treatment of erythroleukemia.